Still plenty of options to control cholesterol, despite Pfizer drug failure

niaspanPfizer Inc.'s new experimental heart drug is dead, but the dual approach the company was testing -- boosting good cholesterol while lowering the bad -- is very much alive, specialists said Monday.

A drug already on the market, Niaspan, raises good cholesterol without serious risks, and a large federal study is testing it with statin medications -- the very thing Pfizer was trying to do before being forced to abandon research on its drug, torcetrapib, over the weekend because of safety problems.

For consumers, the main fallout may be a delay in getting a new medicine that avoids Niaspan's chief side effect, a hot prickly sensation called flushing that patients hate but that can be minimized, doctors said.
Dr. Raymond Gibbons, president of the American Heart Association and a cardiologist at the Mayo Clinic in Minnesota, said it's disappointing when any new drug for heart disease fails, but other research to raise HDL levels will continue.

"There are several other drugs that are used to raise HDL, but more important to recognize is that there are an array of existing drugs for cholesterol problems and the main target is LDL, the bad cholesterol," Gibbons said. "If you are on a statin, people shouldn't feel they are in any danger. We know existing therapies to treat cholesterol are effective."

The Cleveland Clinic's Dr. Steven Nissen, who led one recent study on the doomed Pfizer drug, said the development "does set us back years" in developing an alternative drug. But Dr. Allen Taylor, of Walter Reed Army Medical Center, said it "raises the safety bar for new agents ... to a very high level" because deaths and heart attacks were significantly greater among those taking the experimental Pfizer drug.

Taylor led the most promising study yet of Niaspan plus a statin drug and has consulted for all of the major companies involved in these research efforts.

On Saturday, Pfizer stopped its torcetrapib study after an independent safety board noticed more deaths and other serious complications among patients getting the experimental drug.

For decades, doctors have focused on lowering LDL or bad cholesterol, as the main way to cut the risk of heart problems. Millions of Americans already take statins, sold under such brand names as Lipitor and Zocor, to lower LDL, which ferries fats from food into the bloodstream.

But lots of statin users suffer heart attacks and strokes anyway, so doctors increasingly have been looking at boosting HDL, or good cholesterol -- which escorts fat out of the blood and to the liver to be disposed -- to lower risk further.

Niacin, a type of B vitamin, does this, and Niaspan, made by Kos Pharmaceuticals Inc., is an extended-release version of niacin that minimizes flushing. It has been on the market since the late 1990s, although niacin has been sold as a vitamin for more than 50 years.

At an American Heart Association conference two years ago, Taylor reported that Niaspan plus statin drugs kept blockages in heart arteries from getting worse. There also were fewer heart attacks, deaths, strokes and other problems among those taking Niaspan plus statins vs. statins alone in his study.

Pfizer's torcetrapib appeared to be a much more potent booster of HDL but had "a laser-guided missile approach" in the way it worked that may have made it uniquely dangerous, said Taylor, who served on a Pfizer advisory panel for the drug.

"My suspicion is torcetrapib failed because of its mechanism of action," agreed Dr. Greg Brown of the University of Washington in Seattle, who is leading the big federal study of Niaspan plus the statin Zocor. It involves several thousand patients at 72 medical centers in the United States and Canada.

Taking Niaspan at bedtime along with aspirin and a low-fat snack can minimize the hot flashes, or flushing problem, Taylor said.

Merck & Co. also is testing an HDL-booster: its own extended-release niacin combined with a prostaglandin blocker, a drug to prevent some of the flushing. Drugs called fibrates also raise HDL, but carry risks when combined with statins.

The Washington Post reported that on Sunday experts stressed that the overall concept -- boosting good cholesterol while lowering the bad -- remains promising, but the news about torcetrapib raises disturbing questions about the approach.

"It's a major blow -- a huge setback for the field," Steven Nissen, the president of the American College of Cardiology, said of the halt in Pfizer's research. "Everyone agreed this was an extremely promising approach. This sets back the field by years."

The Post also quoted experts saying the development will require researchers at Pfizer and elsewhere to take a much closer look at similar compounds being developed to determine whether they carry similar risks.

"We'll certainly have to approach all these programs with more caution now as this plays out," said Robert Meyers, a drug safety specialist at the Food and Drug Administration.

Heart disease is the nation's leading cause of death. The number of Americans suffering heart attacks and strokes has been dropping, in part because of the development of cholesterol-lowering statins, which have become one of the most widely used and effective tools in medicine.

"There's a lot of scrambling that's going to be going on to figure out if this [torcetrapib] is a fundamentally flawed compound, or whether this approach is flawed," said Daniel Rader of the University of Pennsylvania.

Even if the approach is flawed, researchers will certainly not abandon the goal of raising HDL, he said.

"I think it is terribly important to emphasize that this development says nothing about the overall strategy," said Rader.